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3-159995457-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000882.4(IL12A):c.660G>A(p.Pro220=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00141 in 1,607,390 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

IL12A
NM_000882.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.40
Variant links:
Genes affected
IL12A (HGNC:5969): (interleukin 12A) This gene encodes a subunit of a cytokine that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-independent induction of interferon (IFN)-gamma, and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity. [provided by RefSeq, Jul 2008]
IL12A-AS1 (HGNC:49094): (IL12A antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 3-159995457-G-A is Benign according to our data. Variant chr3-159995457-G-A is described in ClinVar as [Benign]. Clinvar id is 721071.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.4 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
IL12ANM_001397992.1 linkuse as main transcriptc.558G>A p.Pro186= synonymous_variant 7/7 ENST00000699704.1
IL12ANM_000882.4 linkuse as main transcriptc.660G>A p.Pro220= synonymous_variant 7/7
IL12A-AS1NR_108088.1 linkuse as main transcriptn.1085-1152C>T intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
IL12AENST00000699704.1 linkuse as main transcriptc.558G>A p.Pro186= synonymous_variant 7/7 NM_001397992.1 P1
IL12A-AS1ENST00000497452.5 linkuse as main transcriptn.1085-1152C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00114
AC:
173
AN:
152146
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000410
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00144
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00283
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00135
Gnomad OTH
AF:
0.00479
GnomAD3 exomes
AF:
0.00105
AC:
259
AN:
245692
Hom.:
0
AF XY:
0.00105
AC XY:
140
AN XY:
132844
show subpopulations
Gnomad AFR exome
AF:
0.000251
Gnomad AMR exome
AF:
0.00163
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000166
Gnomad SAS exome
AF:
0.000172
Gnomad FIN exome
AF:
0.00292
Gnomad NFE exome
AF:
0.00112
Gnomad OTH exome
AF:
0.000846
GnomAD4 exome
AF:
0.00144
AC:
2089
AN:
1455126
Hom.:
1
Cov.:
29
AF XY:
0.00136
AC XY:
981
AN XY:
723774
show subpopulations
Gnomad4 AFR exome
AF:
0.000151
Gnomad4 AMR exome
AF:
0.00197
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000127
Gnomad4 SAS exome
AF:
0.000154
Gnomad4 FIN exome
AF:
0.00289
Gnomad4 NFE exome
AF:
0.00154
Gnomad4 OTH exome
AF:
0.00175
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00114
AC:
173
AN:
152264
Hom.:
0
Cov.:
32
AF XY:
0.00120
AC XY:
89
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000409
Gnomad4 AMR
AF:
0.00144
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00283
Gnomad4 NFE
AF:
0.00135
Gnomad4 OTH
AF:
0.00474
Alfa
AF:
0.00110
Hom.:
0
Bravo
AF:
0.00117

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeAug 08, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
Cadd
Benign
1.6
Dann
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56043315; hg19: chr3-159713244; COSMIC: COSV59759606; COSMIC: COSV59759606; API